A variety of techniques have been used to extract specific biological targets from a biological samples obtained from patients or subjects of medical and scientific research. Traditionally, such techniques have required often difficult (and crude) manual dissection of tissue using needles or other micro-manipulation devices to obtain quantities of individual cells identified according to their visible, histological characteristics.
A key emerging challenge in effectively diagnosing patients and treating them is applying protein, nucleotide, drug and other screens to sufficient amounts of purified biological material from patient samples. For example, in order to genetically screen a cancer patient for type of cancer or for effective anti-cancer drugs or therapy, the practitioner must have enough cancer cells so that he or she can run a genetic or drug screen against those cells without being confounded by material from surrounding non-cancerous cells. In a patient sample, only a small fraction of tissue and cells may be cancerous, and those cells may occupy a complex shape in the tissue or biological sample. In order to collect enough genetic material from cancer cells, instead of from surrounding non-cancerous cells, and in order to have a good signal-to-noise ratio (more genetic material from cancerous cells than genetic material from non-cancerous cells), it is advantageous to purify disease materials from patient samples, and that purification must be integrated with subsequent patient analysis, diagnosis, follow up, and treatment.
U.S. Pat. No. 8,597,715 discloses a method of removing a target from a biological sample which involves placing a transfer surface in contact with the biological sample, and then focally altering the transfer surface to allow selective separation of the target from the biological sample. The target is a cell or cellular component of a tissue section and the transfer surface is a film that can be focally altered to adhere the target to the transfer surface. Subsequent separation of the film from the tissue section selectively removes the adhered target from the tissue section. The transfer surface is focally altered by the target (e.g. by antibody binding), and that alteration is then activated to adhere the target to the transfer surface. Such in situ alteration can be achieved by exposing the biological sample to an immunoreagent that specifically binds to the target (or a component of the target). The immunoreagent can alter the transfer surface directly (for example with a heat generating enzyme carried by the immunoreagent), or indirectly (for example by changing a characteristic of the target). Activation can occur for example by illuminating or heating the target to, adhere it to a thermoplastic transfer surface. The immunoreagent can deposit a precipitate in the target that increases its light absorption relative to surrounding tissue, such that the biological specimen can be exposed to light to selectively heat the target. Alternatively, the immunoreagent is an immunofluorescent agent that carries a fluorophore that absorbs light and emits heat. The methods and substrates disclosed in U.S. Pat. No. 8,597,715, and its related patents, U.S. Pat. Nos. 7,695,752, and 7,709,047, are incorporated herein.
Below we disclose methods, devices, and systems for integrating extraction and purification of bio-sample regions and materials with patient analysis, diagnosis, follow up, and treatment.